Certain 7-sydnoneacylamido cephalosporins possessing antibacterial activity have been described and claimed in U.S. Pat. Nos. 3,530,123 and 3,563,983. Additionally, certain 7-tetrazolyacylamido cephalosporins have been described and claimed in U.S. Pat. No. 3,516,997.
In producing the compounds described in the above patents, a 7-aminocephalosporin can be acylated with an appropriate acylating agent so as to obtain the corresponding 7-acylamido cephalosporin derivative. Acylation of the 7-amino group of the cephalosporin to produce the 7-sydnoneacylamido cephalosporin has been accomplished in the above U.S. patents by reacting it will free acid derivative of the appropriate acyl group in the presence of a scavenger for the water which is formed as by-product. Such a scavenger can be, for example, N,N'-dicyclohexylcarbodiimide.
Also, in Naito et al., The Journal of Antibiotics, 21, pages 300-305 (1968), 7-aminocephalosporins were acylated to the corresponding 7-sydnoneacylamido derivatives using sydnone-3-acetyl chloride.
Additionally, U.S. Pat. No. 3,516,997 describes the acylation of a 7-aminocephalosporin by treatment thereof with a mixed anhydride produced from the acid of the selected acyl group and pivaloyl chloride.
The extent of success of the acylation is dependent upon the particular method which is employed as well as upon the structural characteristics of the particular acyl function which is to be attached to the 7-amino group of the cephalosporin.
It has now been discovered that it is possible to achieve a facile and highly successful acylation of the 7-amino group of a 7-aminocephalosporin to produce the corresponding 7-(sydnone-3-acetamido)- or 7-(1-tetrazoleacetamido)- derivative. This acylation involves the use as acylating agent of a specific ester of sydnone-3-acetic acid or 1-tetrazoleacetic acid.